Relative contributions of emphysema and airway remodelling to airflow limitation in COPD: Consistent results from two cohorts (original) (raw)
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Association Between Functional Small Airways Disease and FEV1 Decline in COPD
American journal of respiratory and critical care medicine, 2016
The small conducting airways are the major site of airflow obstruction in COPD and may precede emphysema development. We hypothesized a novel CT biomarker of small airways disease predicts FEV1 decline. We analyzed 1,508 current and former smokers from COPDGene with linear regression to assess predictors of change in FEV1 (ml/year) over 5 years. Separate models for non-obstructed and obstructed subjects were generated using baseline clinical and physiologic predictors in addition to two novel CT metrics created by Parametric Response Mapping (PRM), a technique pairing inspiratory and expiratory CT images to define emphysema (PRMemph) and functional small airways disease (PRMfSAD), a measure of non-emphysematous air trapping. Mean (SD) rate of FEV1 decline in ml/year for GOLD 0-4 was as follows: 41.8 (47.7), 53.8 (57.1), 45.6 (61.1), 31.6 (43.6), and 5.1 (35.8) respectively (trend test for grades 1-4, p<0.001). In multivariable linear regression, for non-obstructed participants, P...
Emphysema in Severe COPD CT Metrics of Airway Disease and
Emphysema in Severe COPD CT Metrics of Airway Disease and http://chestjournal.chestpubs.org/content/136/2/396.full.html and services can be found online on the World Wide Web at: The online version of this article, along with updated information ISSN:0012-3692 ) Background: CT scan measures of emphysema and airway disease have been correlated with lung function in cohorts of subjects with a range of COPD severity. The contribution of CT scan-assessed airway disease to objective measures of lung function and respiratory symptoms such as dyspnea in severe emphysema is less clear. Methods: Using data from 338 subjects in the National Emphysema Treatment Trial (NETT) Genetics Ancillary Study, densitometric measures of emphysema using a threshold of ؊950 Hounsfield units (%LAA-950) and airway wall phenotypes of the wall thickness (WT) and the square root of wall area (SRWA) of a 10-mm luminal perimeter airway were calculated for each subject. Linear regression analysis was performed for outcome variables FEV 1 and percent predicted value of FEV 1 with CT scan measures of emphysema and airway disease. Results: In univariate analysis, there were significant negative correlations between %LAA-950 and both the WT (r ؍ ؊0.28, p ؍ 0.0001) and SRWA (r ؍ ؊0.19, p ؍ 0.0008). Airway wall thickness was weakly but significantly correlated with postbronchodilator FEV 1 % predicted (R ؍ ؊0.12, p ؍ 0.02). Multivariate analysis showed significant associations between either WT or SRWA ( ؍ ؊5.2, p ؍ 0.009;  ؍ ؊2.6, p ؍ 0.008, respectively) and %LAA-950 ( ؍ ؊10.6, p ؍ 0.03) with the postbronchodilator FEV 1 % predicted. Male subjects exhibited significantly thicker airway wall phenotypes (p ؍ 0.007 for WT and p ؍ 0.0006 for SRWA). Conclusions: Airway disease and emphysema detected by CT scanning are inversely related in patients with severe COPD. Airway wall phenotypes were influenced by gender and associated with lung function in subjects with severe emphysema. (CHEST 2009; 136:396 -404) Abbreviations: BMI ϭ body mass index; %LAA ϭ percent emphysema; %LAA-950 ϭ percent emphysema at a threshold of 950 Hounsfield units; NETT ϭ National Emphysema Treatment Trial; Pi10-mm ϭ 10-mm luminal perimeter; SRWA ϭ square root wall area; UCSD SOBQ ϭ University of California, San Diego Shortness of Breath Questionnaire; WT ϭ wall thickness CHEST Original Research COPD 396 Original Research
Respiration, 2012
emphysema score in all patients was 25.6 8 25.4%. There was a weak but significant correlation between the percentage of pulmonary emphysema and numbers of pack/years (R = +0.31, p = 0.024). The percentage of emphysema was inversely correlated with the FEV 1 /FVC ratio before and after bronchodilator use (R = -0.44, p = 0.002, and R = -0.39, p = 0.005), DL CO % (R = -0.64, p = 0.0003) and DL CO /VA% (R = -0.68, p ! 0.0001). A weak positive correlation was also found with TLC% (R = +0.28, p = 0.048). When patients with documented emphysema were considered separately, the best significant correlation observed was between DL CO /VA% and HRCT scan score (p = 0.007). Conclusions: These data suggest that in patients with stable chronic obstructive pulmonary disease of varying severity, the presence of pulmonary emphysema is best represented by the impaired gas exchange capability of the respiratory system.
CT metrics of airway disease and emphysema in severe COPD
Chest, 2009
Background: CT scan measures of emphysema and airway disease have been correlated with lung function in cohorts of subjects with a range of COPD severity. The contribution of CT scan-assessed airway disease to objective measures of lung function and respiratory symptoms such as dyspnea in severe emphysema is less clear. Methods: Using data from 338 subjects in the National Emphysema Treatment Trial (NETT) Genetics Ancillary Study, densitometric measures of emphysema using a threshold of ؊950 Hounsfield units (%LAA-950) and airway wall phenotypes of the wall thickness (WT) and the square root of wall area (SRWA) of a 10-mm luminal perimeter airway were calculated for each subject. Linear regression analysis was performed for outcome variables FEV 1 and percent predicted value of FEV 1 with CT scan measures of emphysema and airway disease. Results: In univariate analysis, there were significant negative correlations between %LAA-950 and both the WT (r ؍ ؊0.28, p ؍ 0.0001) and SRWA (r ؍ ؊0.19, p ؍ 0.0008). Airway wall thickness was weakly but significantly correlated with postbronchodilator FEV 1 % predicted (R ؍ ؊0.12, p ؍ 0.02). Multivariate analysis showed significant associations between either WT or SRWA ( ؍ ؊5.2, p ؍ 0.009;  ؍ ؊2.6, p ؍ 0.008, respectively) and %LAA-950 ( ؍ ؊10.6, p ؍ 0.03) with the postbronchodilator FEV 1 % predicted. Male subjects exhibited significantly thicker airway wall phenotypes (p ؍ 0.007 for WT and p ؍ 0.0006 for SRWA). Conclusions: Airway disease and emphysema detected by CT scanning are inversely related in patients with severe COPD. Airway wall phenotypes were influenced by gender and associated with lung function in subjects with severe emphysema. (CHEST 2009; 136:396 -404) Abbreviations: BMI ϭ body mass index; %LAA ϭ percent emphysema; %LAA-950 ϭ percent emphysema at a threshold of 950 Hounsfield units; NETT ϭ National Emphysema Treatment Trial; Pi10-mm ϭ 10-mm luminal perimeter; SRWA ϭ square root wall area; UCSD SOBQ ϭ University of California, San Diego Shortness of Breath Questionnaire; WT ϭ wall thickness Manuscript
Chronic Obstructive Pulmonary Diseases: Journal of the COPD Foundation, 2022
Background: Forced expiratory volume over one second (FEV1) is central to diagnosis of chronic obstructive pulmonary disease (COPD) but is imprecise in classifying disease burden. We examined the potential of the maximal mid-expiratory flow rate (FEF25-75%) as an additional tool for characterizing pathophysiology in COPD. Objective: To determine whether FEF25-75% helps predict clinical and radiographic abnormalities in COPD. Study Design and Methods: SPIROMICS enrolled a prospective cohort of 2,978 nonsmokers and ever-smokers, with and without COPD, to identify phenotypes and intermediate markers of disease progression. We used baseline data from 2,771 ever-smokers from the SPIROMICS cohort to identify associations between percent predicted FEF25-75% (%predFEF25-75%) and both clinical markers and computed tomography (CT) findings of smoking-related lung disease. Results: Lower %predFEF25-75% was associated with more severe disease, manifested radiographically by increased functional small airways disease, emphysema (most notably with homogeneous distribution), CT-measured residual volume (RV), total lung capacity (TLC), and airway wall thickness, and clinically by increased symptoms, decreased 6-minute walk distance, and increased bronchodilator responsiveness (BDR). A lower %predFEF25-75% remained significantly associated with increased emphysema, functional small airways disease, TLC and BDR after
Relationship between emphysema quantification and COPD severity
Journal of the Medical Association of Thailand = Chotmaihet thangphaet, 2014
To determine the association between emphysema extent from high-resolution computed tomography (HRCT) and the physiological derangement in patients with chronic obstructive pulmonary disease (COPD). A cross-sectional study was undertaken to quantify the emphysema severity in 23 COPD patients by automated HRCT scoring techniques. Correlation with phenotypic characters in term of exercise capacity [Modified Medical Research Council (mMRC) dyspnea scale, and 6-minute walk distance (6MWD)], pulmonary function testing [spirometry (forced expiratory volume in 1 second, FEV1 and forced vital capacity, FVC), and diffusing capacity (DLCO)], were then assessed. Nineteen patients were male and four were female, the mean age was 73 ± 8 years, with the mean FEV1 % predicted of 67.8 ± 25.4. Percentage of inspiratory emphysematous lung volume (%ELVi) had significant negative correlation with %FEV/FVC (r = -0.50, p = 0.016) and DLCO (r = 0.58, p = 0.011). Percentage of expiratory emphysematous lung...
Airflow Limitation and Airway Dimensions in Chronic Obstructive Pulmonary Disease
American Journal of Respiratory and Critical Care Medicine, 2006
Rationale: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation caused by emphysema and/or airway narrowing. Computed tomography has been widely used to assess emphysema severity, but less attention has been paid to the assessment of airway disease using computed tomography. Objectives: To obtain longitudinal images and accurately analyze short axis images of airways with an inner diameter у 2 mm located anywhere in the lung with new software for measuring airway dimensions using curved multiplanar reconstruction. Methods: In 52 patients with clinically stable COPD (stage I, 14; stage II, 22; stage III, 14; stage IV, 2), we used the software to analyze the relationship of the airflow limitation index (FEV 1 , % predicted) with the airway dimensions from the third to the sixth generations of the apical bronchus (B1) of the right upper lobe and the anterior basal bronchus (B8) of the right lower lobe. Measurements and Main Results: Airway luminal area (Ai) and wall area percent (WA%) were significantly correlated with FEV 1 (% predicted). More importantly, the correlation coefficients (r ) improved as the airways became smaller in size from the third (segmental) to sixth generations in both bronchi (Ai: r ϭ 0.26, 0.37, 0.58, and 0.64 for B1; r ϭ 0.60, 0.65, 0.63, and 0.73 for B8).
Contribution of Emphysema and Small Airways in COPD
CHEST Journal, 1996
Background: The contribution and role of emphysema and small airways disease in causing expiratory airflow limitation in COPD is controversial. Methods: We obtained high-resolution thin-section 2-mm CT scans ofthe lung for emphysema grading and lung function in 116 consecutively seen COPD outpa¬ tients with fixed expiratory airflow limitation. In this group, inflated whole lung(s) were subsequently ob¬ tained in 24 patients (23 autopsy, 1 surgery) for mor¬ phologic studies and results compared with lung CT. Airway histologic condition was studied in 17 ofthe 24 patients. Results: There was fair to weak negative correlation between CT emphysema score and either FEVi/FVC percent (r=-0.51, p=0.001) or FEVi percent predicted (r=-0.31, p=0.001). In only 24 ofthe 81 patients (30%) with FEVi less than 50% predicted, the CT emphy¬ sema score was 60 or more, indicating severe emphy¬ sema. In the 24 patients studied, there was a good correlation (r=0.86, p=0.001) between CT and patho¬ logic grade of emphysema. While respiratory bronchi¬ oles (RBs) and membranous bronchioles (MBs) dem¬ onstrated marked morphologic abnormalities, there was a weak correlation with emphysema grade (for RB, r=0.36, p=0.16; for MB, r=0.41, p=0.10) or with FEVi percent predicted (for RB, r=-0.21, p=0.42; for MB, r=-0.28, p=0.28). There was no correlation between emphysema and FEVi percent predicted (r=-0.13, p=0.54). Conclusions: High-resolution CT lung scans are an in vivo surrogate to quantitate moderate to severe mor¬ phologic emphysema. Emphysema does not appear to be primarily responsible for severe expiratory airflow limitation in most patients with severe COPD. There was no correlation between severity of small airway histologic condition and emphysema or FEVi percent predicted. The causes of the lesions responsible for small airways obstruction need to be identified. (CHEST 1996; 109:353-59) Deo=diffusion of carbon monoxide; MB=membranous bronchiole; RB=respiratory bronchiole Key words: COPD; CT lung; diffusing capacity; emphy¬ sema; pulmonary function; small airways disease TPhe pathophysiologic role and contribution of em-¦*¦ physema and small airways abnormalities in fixed expiratory airflow obstruction in COPD remain con¬ troversial.1,2 Previous studies correlating lung function with morphologic abnormalities were limited by the availability of either autopsy specimens or lobes or lungs obtained at surgery. Results indicated small air¬ way morphologic lesions showed good3"8 to poor9"12 correlation with chronic expiratory airflow limitation. Additionally, investigators have concluded that em¬ physema was13"17 or was not2,8'912 the most important
2012
A defi ning characteristic of COPD is expiratory airfl ow limitation due to intrinsic remodeling of the small airways and their dynamic collapse during forced exhalation. 1 In a normal lung, infl ation results in a predictable increase in airway caliber because of the interdependence of parenchyma and airways (the relative change in airway diameter is linearly related with the cube root of lung volume). 2 Emphysema alters this relationship by disrupting airway-parenchymal interdependence. Early work in small animals demonstrated that methacholine-induced bronchoconstriction was increased in elastase models of emphysema, 3 suggesting that the bronchoconstrictive effect of airway smooth muscle activation is opposed by the Background: An increase in airway caliber (airway distensibility) with lung infl ation is attenuated in COPD. Furthermore, some subjects have a decrease in airway caliber with lung infl ation. We aimed to test the hypothesis that airway caliber increases are lower in subjects with emphysemapredominant (EP) compared with airway-predominant (AP) CT scan subtypes. Additionally, we compared clinical and CT scan features of subjects with (airway constrictors) and without a decrease in airway caliber. Methods: Based on GOLD (Global Initiative for Chronic Obstructive Lung Disease) stages and CT scan subtypes, we created a control group (n 5 46) and the following matched COPD groups (n 5 23 each): GOLD-2-AP, GOLD-2-EP, GOLD-4-AP, and GOLD-4-EP. From the CT scans of all 138 subjects, we measured emphysema, lung volumes, and caliber changes in the third and fourth airway generations of two bronchi. We expressed airway distensibility (ratio of airway lumen diameter change to lung volume change from end tidal breathing to full inspiration) as a global or lobar measure based on normalization by whole-lung or lobar volume changes. Results: Global distensibility in the third and fourth airway generations was signifi cantly lower in the GOLD-2-EP and GOLD-4-EP groups than in control subjects. In GOLD-2 subjects, lobar distensibility of the right-upper-lobe fourth airway generation was signifi cantly lower in those with EP than in those with AP. In multivariate analysis, emphysema was an independent determinant of global and lobar airway distensibility. Compared with nonconstrictors, airway constrictors experienced more dyspnea, were more hyperinfl ated, and had a higher percentage of emphysema. Conclusions: Distensibility of large-to medium-sized airways is reduced in subjects with an EP CT scan subtype. Emphysema seems to alter airway-parenchyma interdependence.